Non-migraine Headache Research Articles

494 Association of granuloma annulare with type II diabetes, cigarette smoking, and liver disease: A case-control study

Granuloma annulare (GA) is a cutaneous granulomatous disorder of unknown etiology. There are conflicting reports of associations between GA and a range of systemic diseases. We conducted a retrospective case-control study of GA patients to clarify the relationship of GA with multiple systemic conditions. The electronic medical records of patients age 18 or older who presented to the Johns Hopkins Hospital System between January 1, 2009 and June 1, 2019 were reviewed under IRB approval. Inclusion criteria required a clinical and histopathological diagnosis of GA by a dermatologist. GA patients (n=82) were age, race, and sex matched to controls in a 1:2 ratio. Controls (n=164) presented as outpatients for benign, localized chief complaints. Continuous variables were assessed with a Student’s t-test, and categorical variables with Pearson Chi-squared or Fisher's exact tests. On average, GA patients were 58 ± 16 years old. They were primarily non-Hispanic whites (85%) and women (73%). Patients with GA had a higher incidence of type II diabetes (P=0.0007), liver disease (P=0.0429), non-migraine headache disorders (P=0.0180), and a positive smoking history (P=0.0257) compared to controls. Conflicting with prior reports, no associations were found between GA and dyslipidemia, thyroid disease, or solid organ malignancy. Among GA patients, women were more likely than men to present with ophthalmic conditions (P=0.04), while men were more likely to have concurrent cardiovascular disease (P<0.0001) and type II diabetes (P=0.05). There were no significant differences found in the comorbid conditions of GA patients when separated by race. These results further clarify the comorbidities of GA and suggest potential areas of investigation into its pathogenesis.

Impacts of migraine on the prevalence and clinical presentation of depression: A population-based study

BackgroundA close association has been reported between depression and migraine. However, information concerning the impacts of migraine on the clinical presentation and prevalence of depression in a population-based study is currently limited. MethodsData from the Korean Headache-Sleep Study, a nationwide survey about headache and sleep for adults aged 19-69 years were used. Depression was defined when Patient Health Questionnaire-9 score ≥ 10. ResultsOf 2,695 participants who included in this study, 116 (4.3%), 143 (5.3%), and 1130 (41.9%) had depression, migraine, and non-migraine headache, respectively. Migraine (24/116 [20.5%] vs. 119/2579 [4.7%], p < 0.001) and non-migraine headache (67/116 [58.1%] vs. 1063/2579 [41.3%], p < 0.001) was more prevalent in the group of participants with depression than among participants without depression. Among participants with depression, there was no statistically differences in total Patient Health Questionnaire-9 (PHQ-9) scores among migraine, non-migraine headache, and non-headache groups (median with interquartile range, 12.0 [10.2–18.0] vs. 13.0 [11.0–16.0] vs. 12.0 [10.0–15.2], p = 0.514). Among subcomponent scores of PHQ-9, all subcomponent scores did not significantly differ by headache status except feeling tired or having little energy scores (non-migraine headache 2.0 [2.0–3.0] vs. non-headache 2.0 [1.0–2.0], p = 0.010). LimitationsDiagnosis of depression based on PHQ-9 questionnaire and small sample size in subgroup analyses. ConclusionsParticipants with depression exhibit an increased risk of migraine and non-migraine headache compared with participants without depression. Among participants with depression, the severity of depression did not significantly differ on the basis of headache status.

Effectiveness of low-dose riboflavin as a prophylactic agent in pediatric migraine

BackgroundRiboflavin may prevent migraine episodes; however, there is limited evidence of its effectiveness in pediatric populations. This study investigated the effectiveness of riboflavin and clinical predictors of response in children with migraines. MethodsWe retrospectively reviewed data from 68 Japanese children with migraines, of whom 52 also exhibited another type of headache. Patients received 10 or 40 mg/day of riboflavin. We evaluated the average migraine frequency per month as a baseline and after 3 months of riboflavin therapy to determine the effectiveness and clinical predictors of response. ResultsThe frequency of migraine episodes was significantly lower at 3 months than at baseline (median, [interquartile range], 5.2 (3–7) vs. 4.0 (2–5); p < 0.01). Twenty-five patients (36.7%) showed 50% or greater reduction in episode frequency (responders), while 18 (26.5%) showed a 25%–50% reduction. We compared responders (n = 25) and non-responders (n = 43) and found no significant differences in sex, familial history, riboflavin dose, migraine type (i.e., presence or absence of aura), age at headache onset, or age at consultation. However, non-responders were more likely to have co-morbid non-migraine headaches (odds ratio, 4.11; 95% confidence interval [CI], 1.27–13.33; p = 0.02); this variable was also significant in a multivariate analysis (adjusted odds ratio, 3.8; 95% CI, 1.16–12.6; p = 0.03). Of the co-morbid headache types, only tension headaches were significant (odds ratio, 0.176; 95% CI, 0.04–0.73; p = 0.013). No adverse effects of riboflavin were identified. ConclusionsLow-dose riboflavin is safe and modestly effective for migraines in children. It may be especially beneficial for children without other co-morbid headache types.

Cognitive aging in migraine sufferers is associated with more subjective complaints but similar age-related decline: a 5-year longitudinal study

Objectives and backgroundThe effect of headache on cognitive performance is controversial, due to conflicting results obtained from studies in clinical or population settings. We aimed to understand if migraine and other headaches modify the rates of decline on different cognitive measures, during a 5-year interval.Design and methodA cohort of community dwelling adults (> 50 years) with migraine (MH), non-migraine headaches (NMH) and controls without headache (WoH), was assessed by a comprehensive neuropsychological battery with tests of memory, language and executive functions, repeated 5 years apart. Change in performance between baseline and reevaluation was compared between groups, and controlled for age, gender, literacy and depressive symptoms.ResultsA total of 275 participants (78.5% WoH, 12.7% MH, 8.7% NMH) were reevaluated (average age 70.40 + 8.34 years, 64% females). Cognitive decline or dementia occurred in 11.4%, with a similar proportion among the three groups. Although MH participants had significantly more subjective cognitive complaints (p = 0.030, 95%CI:]-3.929,-0.014[), both MH and NMH subjects showed an age-associated decline identical to controls. Furthermore, migraine features (disease and attack duration, frequency and aura) were unrelated with cognitive performance.ConclusionMigraine and non-migraine headache are not associated with increasing risk of dementia or cognitive decline at an older age although subjects with migraine have more cognitive complaints. Longer longitudinal studies are necessary to understand if this pattern persists for more than 5 years.

Study the biochemical and molecular role of angiotensin converting enzyme in migraine and non-migraine headache

Study the biochemical and molecular role of angiotensin converting enzyme in migraine and non-migraine headache

Migraine, headache, and mortality in women: a cohort study

BackgroundMigraine carries a high global burden, disproportionately affects women, and has been implicated as a risk factor for cardiovascular disease. Migraine with aura has been consistently associated with increased risk of cardiovascular mortality. However, published evidence on relationships between migraine or non-migraine headache and all-cause mortality is inconclusive. Therefore, we aimed to estimate the effect of non-migraine headache and migraine as well as migraine subtypes on all-cause and cause-specific mortality in women.MethodsIn total, 27,844 Women’s Health Study participants, aged 45 years or older at baseline, were followed up for a median of 22.7 years. We included participants who provided information on migraine (past history, migraine without aura, or migraine with aura) or headache status and a blood sample at study start. An endpoints committee of physicians evaluated reports of incident deaths and used medical records to confirm deaths due to cardiovascular, cancer, or female-specific cancer causes. We used multivariable Cox proportional hazards models to estimate the effect of migraine or headache status on both all-cause and cause-specific mortality.ResultsCompared to individuals without any headache, no differences in all-cause mortality for individuals suffering from non-migraine headache or any migraine were observed after adjustment for confounding (HR = 1.01, 95%CI, 0.93–1.10 and HR = 0.96, 95% CI: 0.89–1.04). No differences were observed for the migraine subtypes and all-cause death. Women having the migraine with aura subtype had a higher mortality due to cardiovascular disease (adjusted HR = 1.64, 95%CI: 1.06–2.54). As an explanation for the lack of overall association with all-cause mortality, we observed slightly protective signals for any cancer and female-specific cancers in this group.ConclusionsIn this large prospective study of women, we found no association between non-migraine headache or migraine and all-cause mortality. Women suffering from migraine with aura had an increased risk of cardiovascular death. Future studies should investigate the reasons for the increased risk of cardiovascular mortality and evaluate whether changes in migraine patterns across the life course have differential effects on mortality.

Prevalence of migraine and non-migraine headache and its relation with other diseases in the adults of Aseer Region, Saudi Arabia.

Background and Aims:Headache is a common yet neglected health problem. There is a lack of information about its distribution, disease characteristics and associated co morbidities in Aseer region of KSA. This study aims to estimate the migraine and headache prevalence, its epidemiological and disease characteristics and relation with other co morbid conditions among general population of Aseer region, Saudi Arabia.Methods:A descriptive cross-sectional survey of 1123 adult participants during the period from Apr 2018 to Dec 2018. The questionnaire was sent to total of 1420 participants, but only 1123 agreed to participate and completed the questions (response rate 79.1%). Participants were recruited through an online survey from 4 main cities in Aseer region. Participants who refused were excluded. Adults were invited to answer a 25-question electronic survey to assess the prevalence of headache (migraine and non-migraine) and its relations with other diseases.Results:The participant's ages ranged from 17 to 60 years old, with mean age of 32.4 ± 10 years. No history of frequent headaches was reported by 152 (13.5%) while 833 (74.2%) had non-migraine headache (NMH) and 138 (12.3%) had migraine headache (MH). Female gender (2:1), poor sleep duration, cerebrovascular disease, dyslipidemia, chronic sinusitis and depression showed a significant association with migraine.Conclusions and Recommendations:The current research revealed a high prevalence of headache either migraine or non-migraine, twice as common in females and in those with insufficient sleeping hours. Most headache attacks were associated mainly with light in form of flashes, sensitivity or aggravated episodes.

The Role of Onabotulinum Toxin Type A in the Management of Chronic Non-migraine Headaches.

Objectives: FDA has approved Onabotulinum toxin type A (BoNTA) for prophylactic treatment of chronic migraines. Recent studies have explored its potential new indications, like treating post-traumatic headaches.Patients and Methods: This is a retrospective chart review of 717 patients, who had failed at least two prophylactic treatments and received BoNTA injections at University of Missouri Hospital from July 2014 to June 2017. Patient demographics, headache type, associated symptoms, prophylaxes tried were reported. Patient's pain severity (numeric pain scale) and frequency (number of headache days/month) pretreatment, at 6 months, and at 12 months were collected.Results: For a single headache type, post-traumatic headaches showed reduction in headache pain severity at 6 months (2.9 ± 0.7) compared to pre-treatment (7 ± 0.7). Headache frequency for post-traumatic headaches was also reduced at 6 months (10.6 ± 2.3) and 12 months (5.1 ± 1.2) compared to pre-treatment (25 ± 1.8). For pseudotumor cerebri headaches, pain severity at pretreatment was 6.4 ± 0.6 compared to 2 ± 0.8 at 6 months, and headache days reduced at 6 months (9.8 ± 2.5) and 12 months (6 ± 4) compared to pretreatment (26 ± 2.9). Opioid use reduced by 67 ± 55.4 at 6 months and 133.3 ± 106.6 at 12 months in morphine equivalent units.Conclusions: Onabotulinum toxin type A is effective in treating multiple types of chronic non-migraine headaches.

Risks of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache.

Tinnitus and hearing impairment are prevalent among headache patients. This study aims to investigate the risk of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache. Participants included 43 294 patients with non-migraine headache (non-migraine headache cohort) and 173 176 patients with no headache of any type (control cohort) frequency-matched with respect to 10-year age interval and sex from the Longitudinal Health Insurance Database 2005 of the Taiwan National Health Insurance Research Database. The mean age of the non-migraine headache cohort was 28.4 ± 14.9 years, and 58.5% of this cohort was male. The incidence rates of tinnitus, sensorineural hearing impairment, and sudden deafness were compared between cohorts using the Kaplan–Meier method with the log-rank test. A Cox proportional hazard model was used to examine the association of tinnitus, sensorineural hearing impairment, and sudden deafness with non-migraine headache, with adjustment for all covariates. The combined risk of either tinnitus, sensorineural hearing impairment, or sudden deafness was higher in the non-migraine headache cohort than in the control cohort (adjusted odds ratio [aHR], 2.73; 95% confidence interval [95% CI], 2.62–2.84; p < 0.0001). Subgroup analysis showed that patients in the non-migraine headache cohort were at significantly higher risk of developing tinnitus (aHR, 3.05; 95% CI, 2.91–3.19; p < 0.0001), sensorineural hearing impairment (aHR, 1.89; 95% CI, 1.74–2.05; p < 0.0001), and sudden deafness (aHR, 2.14; 95% CI, 1.77–2.59; p < 0.0001) than were controls. In this population-based study, the risks of tinnitus, sensorineural hearing impairment, and sudden deafness were found to be significantly higher in patients with non-migraine headache than in those without headache.

Occipital nerve stimulation for non-migrainous chronic headaches: a systematic review protocol

BackgroundDefined as a headache lasting at least 15 days per month, chronic headache is reported by 3% of the general population, and a substantial proportion of them are refractory to current therapies. Occipital nerve stimulation (ONS) is a treatment option, but is still considered as a last resort treatment especially because of its invasive nature and the cost associated. Some reviews reported a limited efficacy of ONS for the treatment of migraines, with a high risk of complications. However, results reporting its efficacy and safety on other headache disorders are unclear. The aim of this review is to assess the efficacy and safety of ONS in regards to non-migrainous chronic headaches.MethodsWe will conduct a systematic review and meta-analysis of studies evaluating the use of ONS in comparison to sham stimulation or the best available treatment in patients with chronic headache. MEDLINE, CINHAL, EMBASE, PsycINFO, ECRI Institute Library, WIKISTIM, the Cochrane Library databases, and clinical trial registries will be searched for eligible studies. The review will include adult patients diagnosed with chronic headache excluding migraine. Two independent reviewers will process to the screening of studies according to titles, abstracts, and then full texts. The primary outcome is the overall reduction of head pain severity. The secondary outcomes are rates of reduction in the severity of head pain, headache frequency, and duration, use of medication, impairment, quality of life, healthcare utilization, return to work, and adverse events. Extracted data will include patients’ and procedure characteristics, details on comparative treatment or sham, and clinical outcomes. The risk of bias of the studies will be also independently assessed using the Cochrane risk of bias tools.DiscussionThis systematic review will allow us to better evaluate the potential role of ONS for the treatment of patients with chronic headache that are refractory to less invasive therapies. It will help to determine the degree of safety of ONS. Moreover, it will help to design and conduct future randomized controlled trials focused on patients who may better respond to such treatment.Systematic review registrationPROSPERO CRD42019121623

A prospective study of migraine history and venous thromboembolism in older adults

Unlabelled Box BackgroundLimited evidence suggests that migraine might be a risk factor for venous thromboembolism (VTE). We conducted an epidemiologic study to assess whether migraine history is associated prospectively with VTE or cross sectionally with hemostatic risk markers for VTE. MethodsIn a population‐based US cohort, 11 985 participants free of VTE reported headache symptoms in 1993‐1995. We classified participants as having either migraines with or without aura, severe nonmigraine headaches, or no severe headaches. We followed them through 2015 for incident VTE verified by medical records. ResultsParticipants’ mean age at baseline was 60 years (SD: 6). Eleven percent were classified as having a migraine history (932 without aura and 396 with aura). Over a mean of 18 years and 211 913 person‐years at risk, 688 participants developed VTE. Participants with a migraine history had no greater risk of VTE compared with those free of severe headache (adjusted hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 0.82‐1.36). Those with migraine history with aura had an HR of 1.25 (95% CI: 0.85‐1.85). Self‐reported physician diagnosis of migraine carried an HR of 1.22 (0.96‐1.55). At baseline, those with a history of migraine, furthermore, did not have a higher frequency of elevated hemostatic risk factors or a higher genetic risk score for VTE. ConclusionThis study does not support the hypothesis that migraine history is an important risk factor for VTE in older adults.

Does insomnia modify the association between C-reactive protein and migraine? The Tromsø Study 2015-2016.

The relationship between high sensitivity C-reactive protein and migraine is unclear. The aim of this cross-sectional population-based study was to investigate the association between high sensitivity C-reactive protein and types of headache, and to evaluate the impact of insomnia on this association. A total of 20,486 (63%) out of 32,591 invited, aged ≥40 years or older, participated in the seventh wave of the Tromsø study conducted in 2015-2016 and had valid information on headache, insomnia and high sensitivity C-reactive protein. The influence of insomnia on the association between questionnaire-based diagnoses of headache and elevated high sensitivity C-reactive protein defined as >3.0 mg/L was assessed using multiple logistic regression, estimating prevalence odds ratio with 95% confidence intervals. A total of 6290 participants (30.7%) suffered from headache during the last year. Among these, 1736 (8.5%) fulfilled the criteria of migraine, 991 (4.8%) had migraine with aura, 746 (3.6%) migraine without aura (3.8%), and 4554 (22.2%) had non-migrainous headache. In the final multi-adjusted analysis, elevated high sensitivity C-reactive protein was associated with headache (odds ratio 1.10, 95% confidence interval 1.01-1.20), migraine (odds ratio 1.17, 95% confidence interval 1.01-1.35), and migraine with aura (odds ratio 1.23, 95% confidence interval 1.01-1.53). No association was found between elevated high sensitivity C-reactive protein and migraine without aura or non-migrainous headache. The association between high sensitivity C-reactive protein and migraine was strongly dependent on insomnia status. Among individuals with insomnia, elevated high sensitivity C-reactive protein was associated with migraine (odds ratio 1.49, 95% confidence interval 1.02-2.17), and migraine with aura (odds ratio 1.59, 95% confidence interval 1.03-2.45), whereas no such relationship was found among those without insomnia. In this cross-sectional study, participants with migraine, in particular migraine with aura, were more likely to have elevated high sensitivity C-reactive protein, evident only among those with insomnia.

Parental migraine in relation to migraine in offspring: Family linkage analyses from the HUNT Study.

Migraine is known to run in families. While some clinical studies have indicated that migraine is disproportionally transmitted through the maternal line, this has not been examined in a population-based setting. We utilized a large, population-based cohort study from Norway, the HUNT Study. Using a cross-sectional design, our sample consisted of 13,731 parents and 8970 offspring. Logistic regression was used to calculate odds ratios with 95% confidence intervals for active migraine and non-migrainous headache in offspring, given active maternal or paternal headache. There was a significant association between maternal migraine and offspring migraine (odds ratio 2.76, 95% confidence interval 2.18-3.51). A weaker association ( p = 0.004 for comparison with maternal migraine) was found between paternal migraine and offspring migraine (odds ratio 1.67, 95% confidence interval 1.33-2.28). For non-migrainous headache, there was a significant association between mothers and offspring (odds ratio 1.25, 95% confidence interval 1.10-1.43), but not between fathers and offspring. Parental migraine is associated with offspring migraine, with a stronger association for maternal migraine. This may indicate maternal-specific transmission.

Plasma Calcitonin Gene-Related Peptide: A Potential Biomarker for Diagnosis and Therapeutic Responses in Pediatric Migraine.

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine.Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA.Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, p = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, p = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, n = 47) than those not (183 ± 54 pg/ml, n = 21) (p = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, n = 14 vs. 67 ± 19 pg/ml, n = 6, p = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives.Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Self-medication for migraine: A nationwide cross-sectional study in Italy.

Headache disorders are considered the second leading cause of years lived with disability worldwide, and 90% of people have a headache episode at least once a year, thus representing a relevant public health priority. As the pharmacist is often the first and only point of reference for people complaining of headache, we carried out a survey in a nationwide sample of Italian pharmacies, in order to describe the distribution of migraine or non-migraine type headaches and medicines overuse among people entering pharmacies seeking for self-medication; and to evaluate the association, in particular of migraine, with socio-demographic and clinical characteristics, and with the pathway of care followed by the patients. A 14-item questionnaire, including socio-demographic and clinical factors, was administered by trained pharmacists to subjects who entered a pharmacy requesting self-medication for a headache attack. The ID Migraine™ Screener was used to classify headache sufferers in four classes. From June 2016 to January 2017, 4424 people have been interviewed. The prevalence of definite migraines was 40%, significantly higher among women and less educated people. About half of all headache sufferers and a third of migraineurs do not consider their condition as a disease and are not cared by any doctor. Among people seeking self-medication in pharmacies for acute headache attacks, the rate of definite or probable migraine is high, and a large percentage of them is not correctly diagnosed and treated. The pharmacy can be a valuable observatory for the study of headaches, and the first important step to improve the quality of care delivered to these patients.

Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache.

Current understanding of the origin of occipital headache falls short of distinguishing between cause and effect. Most preclinical studies involving trigeminovascular neurons sample neurons that are responsive to stimulation of dural areas in the anterior 2/3 of the cranium and the periorbital skin. Hypothesizing that occipital headache may involve activation of meningeal nociceptors that innervate the posterior ⅓ of the dura, we sought to map the origin and course of meningeal nociceptors that innervate the posterior dura overlying the cerebellum. Using AAV-GFP tracing and single-unit recording techniques in male rats, we found that neurons in C2-C3 DRGs innervate the dura of the posterior fossa; that nearly half originate in DRG neurons containing CGRP and TRPV1; that nerve bundles traverse suboccipital muscles before entering the cranium through bony canals and large foramens; that central neurons receiving nociceptive information from the posterior dura are located in C2-C4 spinal cord and that their cutaneous and muscle receptive fields are found around the ears, occipital skin and neck muscles; and that administration of inflammatory mediators to their dural receptive field, sensitize their responses to stimulation of the posterior dura, peri-occipital skin and neck muscles. These findings lend rationale for the common practice of attempting to alleviate migraine headaches by targeting the greater and lesser occipital nerves with anesthetics. The findings also raise the possibility that such procedures may be more beneficial for alleviating occipital than non-occipital headaches and that occipital migraines may be associated more closely with cerebellar abnormalities than in non-occipital migraines.SIGNIFICANCE STATEMENT Occipital headaches are common in both migraine and non-migraine headaches. Historically, two distinct scenarios have been proposed for such headaches; the first suggests that the headaches are caused by spasm or tension of scalp, shoulders, and neck muscles inserted in the occipital region, whereas the second suggests that these headaches are initiated by activation of meningeal nociceptors. The current study shows that the posterior dura overlying the cerebellum is innervated by cervicovascular neurons in C2 DRG whose axons reach the posterior dura through multiple intracranial and extracranial pathways, and sensitization of central cervicovascular neurons from the posterior dura can result in hyper-responsiveness to stimulation of neck muscles. The findings suggest that the origin of occipital and frontal migraine may differ.

Migraine with visual aura is a risk factor for incident atrial fibrillation: A cohort study.

ObjectiveMigraine with visual aura is associated with cardioembolic stroke risk. The aim of this study was to test association between migraine with visual aura and atrial fibrillation (AF), in the Atherosclerosis Risk in Communities study.MethodsIn the Atherosclerosis Risk in Communities study, a longitudinal, community-based cohort study, participants were interviewed for migraine history in 1993–1995 and were followed for incident AF through 2013. AF was adjudicated using ECGs, discharge codes, and death certificates. Multivariable Cox proportional hazards models were used to study the relation between migraine and its subtypes with incident AF, compared with controls without headaches. Mediation analysis was conducted to test whether AF was a mediator of migraine with visual aura-associated stroke risk.ResultsOf 11,939 participants assessed for headache and without prior AF or stroke, 426 reported migraines with visual aura, 1,090 migraine without visual aura, 1,018 nonmigraine headache, and 9,405 no headache. Over a 20-year follow-up period, incident AF was noted in 232 (15%) of 1,516 with migraine and 1,623 (17%) of 9,405 without headache. After adjustment for multiple confounders, migraine with visual aura was associated with increased risk of AF compared to no headache (hazard ratio 1.30, 95% confidence interval 1.03–1.62) as well as when compared to migraine without visual aura (hazard ratio 1.39, 95% confidence interval 1.05–1.83). The data suggest that AF may be a potential mediator of migraine with visual aura–stroke risk.ConclusionsMigraine with aura was associated with increased risk of incident AF. This may potentially lead to ischemic strokes.

Physical–Mental Comorbidity of Pediatric Migraine in the Philadelphia Neurodevelopmental Cohort

To examine the associations between headaches and migraine with physical and mental disorders in a large pediatric registry. In total, 9329 youth aged 8-21 years from the Philadelphia Neurodevelopmental Cohort were included. Physical conditions, including headache, were ascertained from electronic medical records and in-person interviews. Modified International Classification of Headache Disorders (ICHD-II) criteria were used to classify migraine symptoms. Forty-two other physical conditions were classified into 14 classes of medical disorders. Mental disorders were assessed using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia. Lifetime prevalence of any headache was 45.5%, and of migraine was 22.6%. Any headache was associated with a broad range of physical disorders, attention-deficit/hyperactivity disorder (OR 1.2 [95% CI 1.1-1.4]), and behavior disorders (1.3 [1.1-1.5]). Youth with migraine had greater odds of specific physical conditions and mental disorders, including respiratory, neurologic/central nervous system, developmental, anxiety, behavior, and mood disorders than those with nonmigraine headache (OR ranged from 1.3 to 1.9). Comorbidity between headaches with a range of physical conditions that have been associated with adult migraine demonstrates that multimorbidity occurs early in development. Comorbidity may be an important index of heterogeneity of migraine that can guide clinical management, genetic investigation, and future research on shared pathophysiology with other disorders.

Self-perceived attention deficit and hyperactivity symptom levels and risk of non-migraine and migraine headaches among university students: A cross-sectional study.

The aim was to evaluate the association of self-perceived levels of attention deficit and hyperactivity symptoms with non-migraine and migraine headaches among university students. We also evaluated their association with migraine aura. Study subjects were all participants in the internet-based Students Health Research Enterprise. Scores were built to evaluate global attention and hyperactivity symptom levels, self-perceived attention deficit levels and self-perceived hyperactivity symptom levels based on the Adult Attention Deficit and Hyperactivity Disorder Self-Report Scale (ASRS v1.1.). We used standardised questions to classify headache and group participants into "no headache," "non-migraine headache," "migraine without aura" or "migraine with aura". A total of 4816 students were included (mean age 20.3 ± 2.8 years; 75.5% women). Compared with participants without headache, we found significant associations between global ADHD scores and migraine. Students in the highest quintile of global ASRS scores had adjusted odds ratio (aOR) of 1.95 (95% CI 1.56-2.45) when compared to the lowest. This association was mainly driven by an association between self-perceived hyperactivity and migraine with aura. The aOR for migraine with aura was 2.83 (95% CI 2.23-3.61) for students in the highest quintile of hyperactivity. No significant association was found for any attention and hyperactivity symptom level measure and non-migraine headache and between self-perceived levels of attention deficit and migraine. Among students in higher education in France, self-perceived levels of attention deficit and hyperactivity symptoms were selectively associated with migraine. The association was strongest for the hyperactivity domain and migraine with aura.

New-onset interictal headache in Persons with epilepsy (PWE): A case–control study

PurposeIn our personal experience, headache is a frequent complaint in Persons with epilepsy (PWE) receiving antiepileptic drugs (AEDs), carbamazepine (CBZ) in particular. There is hardly any systematic study on AEDs-associated headache. We assessed the association of new-onset interictal headache in PWE with CBZ compared with other AEDs and factors associated with it. MethodsTwo thousand PWE on AEDs were screened, and 165 persons having new-onset interictal headache were identified. Eight persons were excluded because of comorbid illnesses that could potentially contribute to a headache. Finally, 157 were recruited for the study. One hundred fifty-seven age- and sex-matched PWE on AEDs, without headache, were recruited as controls. Headache questionnaire based on the International Classification of Headache Disorders (ICHD-II) criteria was used. Demographic factors, seizure characteristics, type and dose of AEDs, findings on electroencephalogram (EEG), and magnetic resonance imaging (MRI)/computerized tomography (CT) were recorded. ResultsAmong PWE with headache, the majority [88 (56.1%)] were on CBZ compared with other AEDs but not significantly different from controls. In 71 (45%) persons, the headache had migrainous character. In both univariate and multivariate analyses, lower seizure frequency and fewer EEG abnormalities were found to be independent predictors of headache. ConclusionsNew-onset interictal headache is a significant issue in PWE; nonmigrainous headache is more common than the migrainous type. Carbamazepine was not found to have any predilection for new-onset interictal headache compared with other AEDs. A lower frequency of seizures and EEG abnormalities in PWE with headache may suggest that seizures contribute less to the development of headache and may further support the hypothesis that AEDs may be significant contributing factors for the headache.